case report reactive thrombocytosis associated with acute...

Hindawi Publishing CorporationCase Reports in CardiologyVolume 2013, Article ID 707438, 3 pageshttp://dx.doi.org/10.1155/2013/707438

Case ReportReactive Thrombocytosis Associated withAcute Myocardial Infarction following STEMI withPercutaneous Coronary Intervention

Nat Dumrongmongcolgul, Charoen Mankongpaisarnrung,Grerk Sutamtewagul, Nattamol Hosiriluck, Timothy Chen, Alexander Trujillo,Nicholas Dcunha, Kenneth Nugent, and Leigh Ann Jenkins

Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Indiana Avenue,Lubbock, TX 79430, USA

Correspondence should be addressed to Nat Dumrongmongcolgul; [email protected]

Received 9 August 2013; Accepted 8 September 2013

Academic Editors: K. Shimada and C. Steinwender

Copyright © 2013 Nat Dumrongmongcolgul et al. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

The etiology of thrombocytosis can be classified into reactive and essential forms. The rate of thromboembolic events is higherin essential thrombocytosis, and these events include strokes, transient ischemic attacks, retinal artery or retinal vein occlusions,digital ischemia, and acute coronary syndrome. In a study of 732 medical and surgical patients with thrombocytosis, 88% hadreactive thrombocytosis. Patients with reactive thrombocytosis do not require cytoreductive medications or antiplatelet treatment.We report a healthy 40-year-old man without any medical problems who developed a new episode of myocardial infarctionassociated with thrombocytosis after an episode of myocardial infarction followed by percutaneous coronary intervention. He hadthrombocytosis, and his platelet function test did not reveal adequate inhibition. To treat his acute coronary syndrome, therapeuticenoxaparin was added, and clopidrogel was substituted with ticagrelor. We decided to start hydroxyurea to reduce platelets counts.Enoxaparin and hydroxyurea were discontinued when platelet count returned to baseline. JAK-2 and BCR/ABL mutations werenegative. This case report highlights a clinical dilemma (reactive thrombocytosis), which is challenging in terms of managementand pathophysiology.

1. Main Document

A 44-year-old man presented to the emergency departmentwith shortness of breath and chest pain. His only cardiovas-cular risk factor was cigarette smoking. Physical examinationrevealed a blood pressure of 82/67mmHg, heart rate of132 beats per minutes, and body temperature of 97.2 F. Hiscardiovascular examination revealed normal first and secondheart sounds, with no jugular venous distention, murmurs,rubs, or gallops. The remainder of his physical examinationwas unremarkable. Initial ECGwas sinus tachycardia withoutischemic ST-T changes.He developed an episode ofwitnessedcardiac arrest with ventricular fibrillation. Cardiopulmonaryresuscitation (CPR) was performed for 40 minutes until thereturn of spontaneous circulation.The initial troponin T was

1.91 ng/mL (0.01–0.03) after the rhythm was reestablished,the electrocardiogram showed sinus tachycardia with ST-segment elevation in I, aVL, V4, V5, and V6. CK-MB was181.4 ng/mL (0.1–0.49), and creatine kinase was 4248 units/L(77–308). Emergency coronary angiogram showed only totalocclusion of left anterior descending artery. Left circumflexcoronary artery and right coronary artery were normal. Per-cutaneous transluminal coronary angioplasty was performedwith a pressure of 8 atmospheres for 14 seconds, and then abare metal stent (Vision 2.75 × 18mm (diameter × length))was implanted in themid third of the left anterior descendingartery. Aspirin, carvedilol, simvastatin, and clopidogrel wereinitiated. After percutaneous coronary intervention (PCI), hewas placed on therapeutic hypothermia protocol for 24 hours.The hospital course was uneventful. He was extubated and

2 Case Reports in Cardiology

Table 1: Complete blood counts in relation to his hospital course.

Admission date 1 6 8 9 12 13 14 15 27 37DC RA HY FU1 FU2

Platelet count k/𝜇L 266 162 212 249 966 851 830 857 372 237White blood cell count k/𝜇L 6.4 6.4 4.8 6.4 10.1 7.0 6.9 2.6 4.5 4.8Hemoglobin g/dL 15.4 11.6 12.1 11.8 12.1 11.6 11.7 12.1 13.1 13.2DC: discharge date, RA: readmission date, HY: hydroxyurea start date, and FU: follow-up date.

On admission After CPR Readmission

Figure 1: As shown, electrocardiogram on admission date wasunremarkable; then, the ST segment elevation developed aftercardiac arrest. NewTwave inversionwas found on readmission date.

finally discharged home after 9 days without neurologicalconsequences. His complete blood count upon dischargewas white blood cell count 6.4 k/𝜇L, hemoglobin 12.1 g/dL,hematocrit 34.9%, and platelet count 349 k/𝜇L.

He was readmitted three days later because of recurrentchest pain at rest, even though the patient had been com-pliant with medication. On admission, physical examinationrevealed a blood pressure of 86/46mmHg, heart rate of 72beat per minutes, body temperature of 97.6∘F, and respiratoryrate of 14/minutes. He was in acute distress; his lungs wereclear to auscultation bilaterally. Hepatosplenomegaly wasnot appreciated. His platelet count was now 966 k/𝜇L, andthe P2Y12 inhibition test (Verifynow) was 11%. (Therapeuticrange ≥20%). His peripheral blood smear showed thrombo-cytosis without basophilia. Troponin T was 0.1 ng/mL, CK-MB was 10.3 ng/mL, and creatine kinase was 97 units/L.Ferritin level was 284 ng/mL. The electrocardiogram showednormal sinus rhythm with unchanged T wave inversionin V4, V5, and V6 but new T wave inversion in V2 andV3 (Figure 1). He was admitted to coronary intensive careunit and underwent cardiac catheterization, which demon-strated a patent stent. Therapeutic dose of enoxaparin wasinitiated, and clopidogrel was substituted with ticagrelor.The hematology service was subsequently consulted becauseof thrombocytosis, and hydroxyurea was initiated with thepending studies for JAK2 and BCR/ABL mutations. Afterthree days of hospitalization, he was discharged home onhydroxyurea, ticagrelor, and therapeutic doses of enoxaparin.Two weeks later, his platelet count was 372 k/𝜇L, and JAK2 and BCR/ABL mutations were negative. Enoxaparin andhydroxyurea were discontinued at that time.

2. Discussion

The etiology of thrombocytosis can be classified into reac-tive thrombocytosis and essential thrombocytosis. Reactivethrombocytosis is caused by elevated thrombopoietin leveland other cytokines, such as interleukin-6. Essential throm-bocytosis is a myeloproliferative disorder characterized bymegakaryocytic hyperplasia in bonemarrow and predisposespatients to vascular complications, such as bleeding or throm-bosis [1]. The rate of thromboembolic events is higher inessential thrombocytosis, and these include strokes, transientischemic attacks, retinal artery or retinal vein occlusions,digital ischemia, and acute coronary syndrome [2]. In a studyof 732 medical and surgical patients with thrombocytosis,88% had reactive thrombocytosis. The most common causesincluded tissue damage from surgery, infection, malignancy,and postsplenectomy status [3]. Of 187 patients diagnosedwith essential thrombocytosis, 50% had at least one episodeof thromboembolic events within nine years of diagnosis[4]. A mutation in the gene encoding Janus kinase 2 (JAK2)is present in 50% of patients with essential thrombocy-tosis; however, it can be found in healthy individuals [5,6]. Thrombosis in postsplenectomized patients commonlyoccurs in portal system with platelet counts more than650 k/𝜇L and has an incidence of approximately 5% [7].Patients with reactive thrombocytosis do not usually requirecytoreductive medication or antiplatelet treatment [8], but,in some circumstances, those with reactive thrombocyto-sis from postsplenectomy and iron deficiency anemia mayrequire antiplatelet treatment given the potential risk ofacute coronary syndrome, stroke, pulmonary embolism, orpulmonary hypertension [9–12].

Our patient developed reactive thrombocytosis afterthe episode of myocardial infarction followed by percuta-neous coronary intervention. Upon discharge, platelet countreturned to normal, but there was a dramatic increase to996 k/𝜇L two days later (Table 1). Our literature search identi-fied only one case report describing reactive thrombocytosisfollowing the episode of myocardial infarction [13]. We thinkthat this is the second reported case of reactive thrombocyto-sis following the myocardial infarction since other potentialcauses seem highly unlikely. However, thrombocytosis in ourpatient was possibly caused by injury from prolonged CPR.

It is well documented that essential thrombocytosis is apredilection to myocardial infarction. Of interest, our patientmight have developed another episode of acute coronary syn-drome (ACS) from reactive thrombocytosis. He had a recur-rent typical angina, new dynamic ST-T changes on V2 and

Case Reports in Cardiology 3

V3, and a new rise of cardiac enzyme with the percentagefrom CK-MB to CK level of greater than 5%. Theoretically,CK-MB level usually returns to baseline in 4 days. With hisacute presentation suggestive of acute coronary syndrome,stent thrombosis was a major concern. As a result, he under-went a second coronary angiography, which demonstrated apatent stentwithout significant thrombosis. Normal coronaryangiograms can be found at 8–12% in patient with acutemyocardial infarction [14]. The pathophysiology of acutecoronary syndrome in this case is probably not from athero-sclerosis or plaque rupture, and we hypothesize that theelevated platelet count from reactive thrombocytosis causedocclusion of a small artery in the myocardium or endo-cardium, resulting in a second myocardial infarction withnormal coronary angiogram. Theoretically, a loading dose of600mg should produce a clopidrogrel peak plasma level in2 hours and peak effect in 6 hours; 75mg dose will produce40% and 60% of inhibition of platelet activity in 3 and 7 days,respectively [15]. Resistance to clopidogrel is well describedwith higher incidence of major cardiac events within 30 daysafter PCI [11].The inhibition of platelet activity in our patientwas only 11% after a loading dose of 600mg of clopidogrel and75mg daily for 10 days, suggesting that his platelets might nothave been suppressed adequately by clopidogrel (drug fail-ure), which led to a recurrent myocardial infarction. Anotherpossibility is that he had primary resistance to clopidogreland developed a second episode of myocardial infarction. Inthis scenario, the reactive thrombocytosis would be an inci-dental finding. We decided to substitute clopidogrel with anewer generation of antiplatelet medication, ticagrelor. Totreat recurrence of ACS, therapeutic dose of enoxaparin wasinitiated to prevent further progression of secondary hemo-stasis. Hydroxyurea, aspirin, and ticagrelor were initiated.Enoxaparin and hydroxyurea were discontinued when hisplatelet count returned to his baseline. This case underscoresthe potentially underrecognized danger of reactive throm-bocytosis. The role of antiplatelet agents or anticoagulantor even cytoreductive medication is not well established.More studies are needed for comprehensive evaluation of thepathophysiology, consequences, and management of reactivethrombocytosis.

References

[1] W. Dameshek, “Some speculations on the myeloproliferativesyndromes,” Blood, vol. 6, no. 4, pp. 372–375, 1951.

[2] Gruppo Italiano Studio Policitemia, “Polycythemia vera: thenatural history of 1213 patients followed for 20 years,” Annalsof Internal Medicine, vol. 123, no. 9, pp. 656–664, 1995.

[3] M. Griesshammer, M. Bangerter, T. Sauer, R. Wennauer, L.Bergmann, andH.Heimpel, “Aetiology and clinical significanceof thrombocytosis: analysis of 732 patients with an elevatedplatelet count,” Journal of Internal Medicine, vol. 245, no. 3, pp.295–300, 1999.

[4] M. Bazzan, G. Tamponi, P. Schinco et al., “Thrombosis-freesurvival and life expectancy in 187 consecutive patients withessential thrombocythemia,” Annals of Hematology, vol. 78, no.12, pp. 539–543, 1999.

[5] K. Lata, N. Madiraju, and L. Levitt, “JAK2 mutations and coro-nary ischemia,” New England Journal of Medicine, vol. 363, no.4, pp. 396–397, 2010.

[6] F. Passamonti, E. Rumi,D. Pietra,M. Lazzarino, andM.Cazzola,“JAK2 (V617F) mutation in healthy individuals,” British Journalof Haematology, vol. 136, no. 4, pp. 678–679, 2007.

[7] K. M. Stamou, K. G. Toutouzas, P. B. Kekis et al., “Prospectivestudy of the incidence and risk factors of postsplenectomythrombosis of the portal, mesenteric, and splenic veins,”Archives of Surgery, vol. 141, no. 7, pp. 663–669, 2006.

[8] M. C. Cheung, L. K. Hicks, and J. Pendergrast, “Thrombocyto-sis,” The New England journal of medicine, vol. 350, no. 24, pp.2524–2525, 2004.

[9] Y. K. Keung and J. Owen, “Iron deficiency and thrombosis:literature review,” Clinical and Applied Thrombosis/Hemostasis,vol. 10, no. 4, pp. 387–391, 2004.

[10] S. Ghaffari and L. Pourafkari, “Acute myocardial infarction ina patient with post-splenectomy thrombocytosis: a case reportand review of literature,” Cardiology Journal, vol. 17, no. 1, pp.79–82, 2010.

[11] M. M. Hoeper, J. Niedermeyer, F. Hoffmeyer, P. Flemming, andH. Fabel, “Pulmonary hypertension after splenectomy?” Annalsof Internal Medicine, vol. 130, no. 6, pp. 506–509, 1999.

[12] P. N. Khan, R. J. Nair, J. Olivares, L. E. Tingle, and Z. Li,“Postsplenectomy reactive thrombocytosis,” Baylor UniversityMedical Center Proceedings, vol. 22, no. 1, pp. 9–12, 2009.

[13] B. wilkerson and S. Elkins, “Clinical significance of reactivethrombocytosis after acute myocardial infartction subsequentstent placement,” A Retrospective Chart Review, SoutnernSociety for Clinical Investigation, New Orleans, La, USA, 2004.

[14] A. Cortell, J. Sanchis, V. Bodı́ et al., “Non-ST-elevation acutemyocardial infarctionwith normal coronary arteries: predictorsand prognosis,” Revista Espanola de Cardiologia, vol. 62, no. 11,pp. 1260–1266, 2009.

[15] R. Hall and C. D. Mazer, “Antiplatelet drugs: a review of theirpharmacology and management in the perioperative period,”Anesthesia and Analgesia, vol. 112, no. 2, pp. 292–318, 2011.

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